The human microbiome plays an important role in both health and disease. While the majority of microorganisms inhabiting the gastrointestinal system of humans and animals have a beneficiary role in, for example, aiding digestion of important nutrients, it is known that a minority of otherwise previously considered “commensal” organisms play a role in the pathogenesis of various diseases.
Irritable Bowel Syndrome (IBS) affects an estimated 30 million people in the United States alone. IBS is a functional gastrointestinal (GI) disorder that results in abdominal pain and/or discomfort, along with changes in bowel habits. IBS is classified into four subtypes based on a person's stool consistency: constipation-associated IBS (IBS-C); diarrhea-associated IBS (IBS-D); mixed (or alternating) IBS (IBS-M or IBS-A); and unsubtyped (or unspecified) IBS (IBS-U).
Recent studies have suggested that certain methane producing microorganisms inhabiting the gut known as methanogens may play a causative role in constipation. Specifically, studies suggest a link between intestinal methane (CH4) production and constipation in IBS-C as well as chronic idiopathic constipation (CIC). Methane (CH4) production in humans is due to methanogenic archaea in the intestine. These organisms serve a critical biological function by removing the by-products of bacterial fermentation of polysaccharides, notably hydrogen gas (H2) and short-chain fatty acids (SCFAs). The dominant methanogen inhabiting the human gut is the archaea, Methanobrevibacter smithii (M. smithii). In vitro susceptibility testing has demonstrated that methanogens such as M. smithii are highly resistant to most classes of antibiotics. Further, complete eradication of intestinal methanogens via a single course of therapy is unlikely using broad spectrum antibiotics, leading to methanogen recolonization and methanogenesis returning to pathogenic levels. Continuous use of antibiotics is associated with various side effects and increased risk of developing antibiotic resistance. Further still, long-term use of antibiotics may disrupt the otherwise potentially beneficial bacterial intestinal microbiome and gastrointestinal flora.
There remains a need for safe and effective approaches for the long term suppression of enteric methanogenesis and/or excessive methane production in the treatment of diseases such as IBS.